Maternal undernutrition programs the apelinergic system of adipose tissue in adult male rat offspring.

Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring's WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.

Serum-stimulated cell cycle entry promotes ncOGT synthesis required for cyclin D expression.

Nuclear and cytoplasmic O-GlcNAc transferase (OGT) is a unique and universally expressed enzyme catalyzing O-GlcNAcylation of thousands of proteins. Although OGT interferes with many crucial intracellular processes, including cell cycle, only few studies have focused on elucidating the precise role of the glycosyltransferase during cell cycle entry. We first demonstrated that starved MCF7 cells reincubated with serum quickly induced a significant OGT increase concomitantly to activation of PI3K and MAPK pathways. Co-immunoprecipitation experiments performed upon serum stimulation showed a progressive interaction between OGT and ß-catenin, a major factor in the regulation of cell cycle. OGT expression was also observed in starved HeLa cells reincubated with serum. In these cells, the O-GlcNAcylation status of the ß-catenin-2XFLAG was increased following stimulation. Moreover, ß-catenin-2XFLAG was heavily O-GlcNAcylated in exponentially proliferating HeLa cells when compared to confluent cells. Furthermore, blocking OGT activity using the potent inhibitor Ac-5SGlcNAc prevented serum-stimulated cyclin D1 synthesis and slightly delayed cell proliferation. At last, interfering with OGT expression (siOGT) blocked cyclin D1 expression and decreased PI3K and MAPK activation. Together, our data indicate that expression and catalytic activity of OGT are necessary and essential for G0/G1 transition.